Archives of pathology & laboratory medicine最新文献

Context.—: Breast pathology reports include many important details to guide clinical management. Reports with missing critical data elements are commonly seen in non-subspecialized pathology practices. The use of synoptic templates has been shown to improve pathology reports. Although synoptic templates are readily available from professional societies, many are not tailored to low-resource settings.

Objective.—: To perform an assessment of current breast pathology reporting at 3 referral hospitals in sub-Saharan Africa and design a locally adapted breast cancer synoptic template.

Design.—: We conducted semi-structured interviews with key stakeholders involved in breast cancer care, including pathologists, radiologists, oncologists, and surgeons, from Nigeria, Tanzania, and Mozambique. Moreover, each stakeholder reviewed a preliminary synoptic template that was compiled by using templates from the College of American Pathologists, Royal College of Pathologists, and International Collaboration on Cancer Reporting and was asked to score each data element as essential, optional, or exclude. A locally adapted synoptic template was then designed from the needs assessment. Using the adapted templates, a retrospective review of breast cancer pathology reports from 2020 to 2022 was conducted to determine the completeness of reports at the 3 institutions.

Results.—: A total of 17 physicians were interviewed. Review of pathology reports revealed that none of the reports across all 3 sites contained all data elements considered essential by local physicians.

Conclusions.—: There is an urgent need to improve breast pathology reporting in sub-Saharan Africa. Development and implementation of synoptic templates in collaboration with key stakeholders has the potential to improve pathology reporting practices in low-resource settings.

Context.—: Lactational lesions of the breast encompass a wide range of entities, ranging from physiologic changes to aggressive malignant tumors. Topics discussed under this umbrella include lactational change, galactocele, mastitis (acute and non-lactational), lactational adenoma, and pregnancy and lactation-associated breast carcinoma. Although the literature suggests that the histopathology of atypia and carcinoma in this context is similar to that in patients of comparable age without associated pregnancy or lactation, diagnosing these on core needle biopsies may be difficult, particularly in the presence of concurrent mastitis.

Objective.—: To review the clinical, radiologic, and specific histopathologic features of lactational lesions of the breast, their differential diagnoses, and challenging aspects as frequently encountered on core needle biopsies.

Data sources.—: The existing scientific and clinical literature from PubMed search as of August 2024 is the primary source of the review. Select cases of pregnancy and lactation-associated lesions from the Thomas Jefferson Hospital breast pathology archives are included and discussed in this review.

Conclusions.—: Accurate diagnosis of pregnant and lactating patients with breast lesions requires clinical, radiologic, and histopathologic correlation. Careful examination of biopsy cores and maintaining a high index of suspicion, even without clear radiologic findings, are essential for identifying atypia. When significant acute mastitis and overlapping secretory/lactational changes complicate the characterization of atypia, requesting additional tissue, using appropriate immunohistochemical stains, or deferring to excisional biopsy is appropriate. Awareness of these entities, given their varied prognoses and the sociopsychological challenges of postpartum and lactation, is crucial for guiding effective management.

Context.—: "Atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) cytology is uncommon (0.16%-0.43%). The reported risk of high-grade dysplasia varies hugely (12.00%-70.00%), making management challenging. Primary human papillomavirus (HPV) screening requires an updated understanding of ASC-H.

Objective.—: To review ASC-H colposcopic and histologic comparators, and management outcomes, to help guide future management.

Design.—: A 1-year retrospective analysis of new ASC-H-associated visits to a large colposcopy unit in Ireland in 2022 was performed.

Results.—: The incidence of new ASC-H referrals was 3.63% (97 of 2672). The sensitivity of colposcopy for detection of high-grade changes (cervical intraepithelial neoplasia [CIN]2+) is 69.39% (34 of 49) and the specificity is 43.18% (19 of 44). The positive predictive value is 64.15% (34 of 53) and the negative predictive value is 37.50% (15 of 40). High-grade dysplasia was identified in 53.26% (49 of 92) and adenocarcinoma in situ in 2.17% (2 of 92) of cases. Excisional treatment was performed for 52.58% (51 of 97) and cold coagulation for 12.37% (12 of 97). The test-of-cure result was HPV negative for 84.13%. High-risk HPV and abnormal cytology was seen in 9.52% (6 of 63) of cases, thus all required a second test-of-cure smear.

Conclusions.—: ASC-H with high-risk HPV has a 55.43% (51 of 92) risk of high-grade dysplasia, thus timely colposcopy and biopsy is imperative. Treatment was curative in 84.13% (53 of 63) to 96.83% (61 of 63) of cases so it is an effective management strategy. Conservative management of selected cases may be a reasonable option.

Context.—: In 2018, an evidence-based guideline was published by the College of American Pathologists to develop recommendations for the testing, application, interpretation, and reporting of high-risk human papillomavirus and surrogate marker tests in head and neck carcinomas. Substantial new evidence has prompted a review, including data on human papillomavirus (HPV) in nonoropharyngeal anatomic sites, HPV global rates, p16 immunohistochemistry, and HPV testing performance in cytology specimens, and performance of p16 immunohistochemistry as a surrogate marker.

Objective.—: To assess research published since the release of the original 2018 guideline and to update evidence-based recommendations for HPV testing in head and neck carcinomas.

Design.—: The College of American Pathologists convened a panel of experts to update the guideline following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The expert panel defined the key questions and performed a systematic review of the literature. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, recommendations were updated on the basis of available evidence, certainty of that evidence, and key judgments.

Results.—: Seven strong recommendations, 4 conditional recommendations, and 5 good practice statements are offered in the guideline update.

Conclusions.—: The updated guideline statements provide direction on the nature of HPV testing in various head and neck specimens (including key updates based on new research on sinonasal squamous cell carcinoma) and expanded guidance on specific scenarios and practice settings. The goal is to improve and standardize, where possible, HPV testing across diverse pathology practice settings and different countries.

Context.—: In colorectal cancer (CRC), the tumor microenvironment includes cancer-associated fibroblasts and a variety of immune cells, which are increasingly recognized for their prognostic significance.

Objective.—: To evaluate the tumor microenvironment in CRC using methodologies applicable in routine pathologic practice.

Design.—: A comprehensive evaluation of the local immune response and tumor to stroma ratio (TSR) was performed in 930 CRC cases by thoroughly reviewing the whole hematoxylin-eosin (H&E) slides. Local immune responses were assessed using peritumoral inflammatory infiltration (Klintrup-Mäkinen and modified Klintrup-Mäkinen methods), intratumoral stromal tumor-infiltrating lymphocytes (TILs; International TILs Working Group system and deep stromal TIL system), and Crohn-like lymphoid reaction (CLR).

Results.—: In the multivariate analysis, age (>68 years), stage III-IV, microsatellite stability, signet ring cell/undifferentiated carcinoma, extramural venous invasion, high TSR (>50%), and CLR were independent prognostic factors for disease-specific survival. Excluding microsatellite stability, these factors also served as significant prognostic indicators for progression-free survival. Among the 4 methods for measuring local immune response, evaluating the proportion of TILs within the deepest intratumoral stroma was an independent predictor of progression-free survival.

Conclusions.—: We suggest that evaluating CLR, TSR, and stromal TILs on hematoxylin-eosin-stained slides represent a practical and straightforward approach with significant prognostic value.

Context.—: Colorectal lesions with neural differentiation encompass various entities, often presenting with overlapping histologic or immunohistochemical profiles. Most research has focused on single entities, lacking a comprehensive comparative analysis of these lesions.

Objective.—: To characterize and compare colorectal lesions with neural differentiation.

Design.—: This study retrospectively examined cases of neural or neural-related colorectal lesions diagnosed between 2004 and 2020 across 2 institutions, analyzing clinical, histologic, and endoscopic features.

Results.—: The cohort included 634 lesions from 593 patients (269 males and 324 females; mean age, 57 years; range, 13-85 years). Most patients were asymptomatic (83%, 490 of 593) and had solitary lesions (92%, 545 of 593), predominantly polypoid or nodular (96%, 610 of 634). Common types included benign fibroblastic polyp/perineurioma (n = 231 of 634, 36%), mucosal Schwann cell hamartoma (n = 203, 32%), and ganglioneuroma (n = 146, 23%), mostly centered in the mucosa (99%, P < .001) of the left colon (n = 318, P < .001). In contrast, granular cell tumors (n = 31, 5%) often involved the submucosa (n = 26, 84%; P < .001) of the cecum and ascending colon (n = 23, 74%; P < .001). Rare lesions like schwannoma (n = 13 of 634, 2%) and neurofibroma (n = 5 of 634, 1%), were found in various sites. A subset of patients (n = 48, 8%) had synchronous and/or metachronous lesions. Of these, 23 (48%) had genetic evidence of a syndromic manifestation (P < .001), with multiple ganglioneuromas in Cowden syndrome (n = 16) being the most common scenario.

Conclusions.—: This is the largest comparative study of neural colorectal lesions, highlighting lesion types' association with colon segments and histologic layers. Multifocal presentations, though rare, are usually linked to genetic syndromes.

Context.—: Maternal SARS-CoV-2 infection has been associated with increased adverse events in the mother, as well as increased stillbirths (11.5 per 1000), spontaneous abortions, and premature delivery. Clinical symptomatology, or the lack thereof, does not appear to be directly related to fetal or neonatal complications. SARS-CoV-2 placentitis is now recognized as the culprit, and the presence of the virus in the syncytiotrophoblasts of the placenta has emerged as a significant predictor of fetal compromise.

Objective.—: To provide a review of the clinical presentation and outcomes, morphologic characteristics, detection methods, and differential diagnosis of SARS-CoV-2 placentitis.

Data sources.—: A case of placental pathology in a patient with COVID-19 infection at the University of Michigan, as well as a review of the available literature through a search of PubMed and Google Scholar.

Conclusions.—: SARS-CoV-2 placentitis is a well-documented outcome of symptomatic and asymptomatic COVID-19 infection during pregnancy. It can disrupt placental function and lead to severe outcomes in the neonate, including growth restriction and stillbirths. Chronic histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis, when present together, may act as a morphologic signature of SARS-CoV-2 placentitis. The histologic differential diagnosis includes massive perivillous fibrin deposition (MPFD)/maternal floor infarction (MFI), chronic villitis of unknown origin, or other infectious villitides. Immunohistochemistry and RNA in situ hybridization are specific to the viral antibodies and RNA, respectively, and are essential for classification.

Context.—: Primary angiitis of the central nervous system is a rare vasculitis that affects small parenchymal and leptomeningeal vessels in the brain and spinal cord. As brain biopsy remains the gold standard in diagnosis, the diagnostic approach to brain biopsies for vasculitis is well described. However, a significant minority of brain biopsies for central nervous system (CNS) vasculitis identify alternative diagnoses. Therefore, it is critical to be aware of the spectrum of infectious, inflammatory, and neoplastic diseases that may enter into the differential diagnosis of a biopsy for potential CNS vasculitis and recognize the pathologic patterns that characterize these diseases.

Objective.—: To review the broad diagnostic considerations in evaluating a biopsy for potential CNS vasculitis, with an emphasis on a pattern-based approach and diagnostic tools used to evaluate other entities in the differential diagnosis.

Data sources.—: This review is based on the clinical experience of the authors and a review of the literature.

Conclusions.—: A diagnosis of CNS vasculitis is dependent on the identification of transmural inflammation and vascular wall damage, preferentially affecting leptomeningeal and superficial cortical vessels. Where a diagnosis of vasculitis is not made, granulomatous, lymphocytic, and necrotizing patterns of inflammation present alternative differential diagnoses. The appropriate application of immunohistochemistry, special stains, and other diagnostic tools is critical in resolving these diagnoses.

Context.—: The VENTANA FOLR1 (FOLR1-2.1) RxDx (FOLR1 CDx) assay, developed by Roche Tissue Diagnostics, is a Food and Drug Administration-approved immunohistochemical assay intended for use in the assessment of folate receptor α (FRα) expression in formalin-fixed, paraffin-embedded epithelial ovarian, fallopian tube, and primary peritoneal tumor specimens. No published reports have compared the performance of other available FRα antibodies with the approved FOLR1 CDx.

Objective.—: To assess the performance of research FRα laboratory-developed tests compared with the FOLR1 CDx.

Design.—: The performance of 6 FRα-targeting antibodies was compared with the approved FOLR1 CDx in normal fallopian tube specimens. Two antibodies were selected for further assessment and compared with the FOLR1 CDx in ovarian tumor specimens.

Results.—: Of the 6 antibodies tested, 4 displayed a lack of specific membrane staining and/or high background, whereas 2 antibodies, produced by Leica Biosystems and Biocare Medical, respectively, exhibited specific and sensitive FRα staining. When assessed for their ability to correctly identify FRα-positive samples (per the FOLR1 CDx label, ≥75% of viable tumor cells with moderate and/or strong membranous staining intensity), both assays overpredicted FRα positivity compared with the FOLR1 CDx in archival ovarian tumor samples.

Conclusions.—: These data highlight the need for caution in antibody selection when developing immunohistochemistry-based assays, as some antibodies failed to cleanly and specifically identify FRα expression. We identified 2 antibodies appropriate for further investigation; however, as developed, these antibodies may overselect patients for treatment with FRα-targeted therapies.

Context.—: Surgery for Hirschsprung disease includes resection of the aganglionic bowel and adjacent transition zone (ganglionic bowel with partial circumferential aganglionosis, myenteric hypoganglionosis, and/or submucosal nerve hypertrophy). Pathology practices, including intraoperative frozen sections and sampling of resection specimens and accurate recognition and reporting of transition zone histopathology, are necessary to both prevent and diagnose incomplete resection.

Objective.—: To identify opportunities to improve pathology practice related to Hirschsprung disease.

Design.—: Surgical pathology reports and histology slides from Hirschsprung disease resections performed on 35 patients (25 institutions) were reviewed. Data included what type of analyses were performed on proximal resection margins (eg, intraoperative frozen section), how resections were sampled for histology, and how the results were reported. Slides were assessed for features of transition zone histology and the findings compared with those in the original surgical pathology reports.

Results.—: The length of the resected ganglionic bowel was stated or calculable in 18 of 35 cases (51%) and most pathology reports did not address the presence or absence of transitional zone histology at the proximal surgical margin. Intraoperative frozen section evaluations of the proximal margin were performed in 8 of 35 cases (23%); 1 or more features of transition zone were present in 3 of these but not documented. Among the remaining 27 patients, transition zone histology was present in 9 (33%) but not reported.

Conclusions.—: Pathologists need to understand transition zone histology and to implement methods to enhance accurate and timely diagnosis. Specific recommendations are provided here to achieve these goals.